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Mastocytosis is a group of disorders characterized by the accumulation of mast cells in various tissues. In this article we report an interesting case of cutaneous mastocytoma in a 3-month-old infant. We describe two episodes characterized by an exacerbation of the skin lesion with the typical Darier’s sign. Both of them occurred after breastfeeding. In both episodes, the mother had eaten shrimps before the breastfeeding. This peculiar case, difficult to understand regarding its pathogenesis, was successful resolved just with dietary prescription given to the breast feeding mother.

The skin immune system is composed of a vast network of immune cells, including lymphocytes, macrophages, neutrophils, dendritic cells and Langerhans cells, which not only are involved in inflammatory responses but also contribute to homeostatic function and may participate in the various steps of carcinogenesis. Many studies support the notion that innate immunity has a key role in the development, growth and prognosis of cutaneous malignant melanoma (MM), through the release of pro- and/or anti-inflammatory cytokines and tumour growth factors. The tumour environment in a major subset of cutaneous MM shows evidence of a T cell-infiltrated phenotype, but there is less known about the presence and the phenotype of other immune system cells. Response to immunotherapy is largely correlated with the presence of T cells in the tumour microenvironment, while the regulation exerted by stromal components such as macrophages and mast cells has been less investigated. In the current report, we review the recent literature, focusing our attention on the role of macrophages, dendritic cells, mast cells and natural killer cells in orchestrating MM progression, to better understand tumour immunobiology. The identification of new therapeutic targets and the application of approaches aimed at modulating crosstalk between immune and tumour cells, could have a crucial impact on immunotherapy and result in better clinical outcome. We hope this review will be helpful in cutaneous MM research.

Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun-exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

Actinic keratoses (AK) are pre-neoplastic lesions related to an excessive ultraviolet exposure that represent an emerging issue in the area of skin diseases which undergo high risk for developing squamous cell carcinoma (SCC). In this open study, we tested the safety efficacy profile of sequential ablative laser and Ingenol Mebutate gel (IngMeb). Thirteen patients with a total of 99 lesions were selected for this open study. When multiple lesions on the same area were found, the treatment area was split in half. In one group, fractional CO2 laser microablative treatment was performed the day before three daily applications of IngMeb 150 lg/g; the other group received IngMeb without previous laser ablation. Fifty-six lesions were treated with laser and IngMeb and a total of 43 lesions in the second group were treated with IngMeb alone. Results at the 12-week follow-up visit showed that a clearance rate of 50/56 (89.2%) had been achieved. On the side that was not pre-treated with laser, 31 out of 43 lesions were cleared (72.1%). In our opinion, ablative fractional laser treatment could improve topical treatment of AKs, or provide a further therapeutic option for resistant patients.

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual’s diagnosis and/or help clarify risk in healthy populations., Diagnostics: Proton state of secreted proteins in blood helps identify cancer A blood test that measures whether molecules secreted by cells contain titratable proton atoms can accurately discriminate between patients who have cancer and those who don’t. Titratable species may in turn influence the protonation state of a solution, i.e. the number of protons added to and the net charge of that solution. A team led by Natalia Malara from University Magna Graecia in Catanzaro, Italy and Enzo Di Fabrizio from the King Abdullah University of Science and Technology in Thuwal, Saudi Arabia, Francesco Gentile from the University Federico II in Naples, Italy, and Nicola Coppedè from the Institute of Materials for Electronics and Magnetism in Parma, Italy, created an eletrochemical device that can detect faulty metabolism by quantifying the proportion of secreted proteins with and without extra protons—an indicator of abnormal cell division, proliferation and invasion. The researchers tested the device on blood samples from patients with solid tumors and healthy controls. The method identified cancer patients with a high degree of accuracy. If the findings are confirmed in larger trials, the test could help with the screening, diagnosis and management of cancer.

BACKGROUND Dermatofibrosarcoma protuberans is a malignant tumor that affects exclusively the skin. It is a low-grade malignant tumor of subcutaneous tissues, characterized by a local recurrence but it seldom metastasizes. This study aimed to evaluate the impact of different clinical parameters on disease free survival and overall survival of dermatofibrosarcoma protuberans patients. METHODS A retrospective study of data including seventeen cases of dermatofibrosarcoma protuberans (eleven male, six female) retrieved from the files of the Dermatology Clinics of La Sapienza University, Rome. We evaluated three clinical parameters (age, sex and anatomic site of the primary tumor) using the Kaplan-Meier product and the Log-Rank Test. RESULTS The results highlighted that patients with an age ≤49 years showed a median disease free survival of 36 months, while patients with an age ≥50 years of 4 months (P

Background The anti-BAFF monoclonal antibody, belimumab, was approved about five years ago by the US Food and Drug Administration for the treatment of adult SLE patients. The utility of belimumab for management of resistant systemic lupus erythematosus (SLE) has been demostrated but concerning skin manifestations only scarce evidences have been reported. We describe our experience of using this new drug for the successful management of recalcitrant cutaneous lupus. Case report A 38-year-old man with a five year history of SLE presented, in May 2017, at our outpatient clinic for a disease flare with severe cutaneous involvement. On examination the patient presented malar rash and erythematous-infiltrated discoid lesions in the region of head and neck and erythematosus papules also on the extensor surface of the hands. Additional tests showed also systemic involvement by detecting low levels of C3 and C4, leukopenia (WBC 3000/µL) and positivity of ANA (1:1280 by IFI) and anti-dsDNA (42.8 UI/ml by ELISA, nv Conclusion In this case report, the addition of belimumab to steroid monotherapy, in patient who failed previous immunosuppressive treatment improved the signs and symptoms of refractory cutaneous lupus. This report highlights the utility of belimumab for the treatment of severe skin involvement in SLE refractory to conventional therapies. Additional studies should be performed to assess the use of belimumab in the treatment of cutaneous lupus.

Actinic keratosis (AK) is a clinical condition characterized by keratinocytic dysplastic lesions of the epidermis, affecting individuals chronically exposed to sunlight. Topical therapies allow the treatment of a whole area of affected skin and currently include diclofenac sodium gel, 5-fluorouracil cream, 5-fluorouracil and acetylsalicylic acid solution, imiquimod cream, and ingenol mebutate gel. Due to the comparable efficacy of 3% diclofenac, ingenol mebutate, and 3.75% imiquimod in treating AK multiple lesions, a pharmacoeconomic evaluation of cost-effectiveness of the three treatments was needed. A cost-efficacy analysis comparing 3% diclofenac sodium with ingenol mebutate and 3.75% imiquimod was performed. In this analysis, efficacy data were combined with quality-of-life measurement derived from previous studies as well as the costs associated with the management of these lesions in Italy. Patients’ demographics and clinical characteristics were assumed to reflect those from the clinical studies considered.

Scleroderma is divided into a systemic form called systemic sclerosis and a localized form also called morphea. According to 2013 ACR/EULAR Classification Criteria for Systemic Sclerosis, developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for a patient to be classified as having scleroderma. Histological examination is not included in the diagnostic criteria and is not routinely performed. Skin biopsy is recommended only in the case of diagnostic doubt with other scleroderma like disorders (scleromyxedema, scleredema, nephrogenic systemic fibrosis). Alternatively, skin biopsy is also often performed for research purposes. Indeed, the first step analysis of new cytokines or pathways that may contribute to the pathogenesis of the disease requires the evaluation of their expression or activation in the skin of scleroderma patients compared to healthy controls. The histological picture of the skin in bot localized and systemic scleroder shows initially microvascular alterations and chronic inflammation while in the more advanced stages skin fibrosis prevails. Localized scleroderma (LS) or morphea includes a number of subtypes which are classified more according to their clinical presentation rather than histopathological pictures. However, some histopathologic changes may be useful in differentiating each entity from the others and from other sclerodermoid disorders.

The sun plays a major role in prematurely aging our skin. Our skin is at the mercy of many forces as we age: sun, harsh weather, and bad habits. But we can take steps to help our skin stay supple and fresh-looking. Sunlight is a major cause of skin aging. The increasing knowledge of the genetic bases of several common multifactorial diseases paves the way to personalized medicine that means preventive and therapeutic interventions that are tailored to individuals on the basis of their genetic profiles. The aging process, as well as multi factorial diseases, depends on a complex crosstalk between intrinsic (genetic and hormonal) andextrinsic (nutrition, lifestyle etc.) factors. Skin changes are the most visible signs of senescence process, and a field of increasing interest ina society that places more and more interest in appearance and beauty. skin disease characterized by increased trans-epidermal water loss and skin barrier abnormalities and disruption. On this subject, numerous environmental events such as: chemical injuries, traumatic wounds, UV exposure and genomic characteristics can compromise the barrier activity. To date, the mutational spectrum of FLG gene comprises different variations that show an ethno-specific distribution profile, especially among north European and Mediterranean populations. The study was conducted in 100 Italian volunteers, with an age between 21 and 66 years old (23 males and 77 females). All selected patients were Caucasian (people with European origin), belonging to Fitzpatrick skin type 2 and 3. Subjects underwent medical history and clinical examination; exclusion criteria included systemic diseases or presence of genetic diseases which were clinically evident. All patients signed written informed consent. The examination of each subject was conducted using a lifestyle questionnaire and, to evaluate the impact of lifetime sun exposure (LSE), using the Sun Exposure and Behavior Inventory (SEBI). For the aging process, like to multi-factorial and polygenic diseases, is known that single genetic polymorphism has only a modest effect since the interaction of each gene and its polymorphism with other ones (gene-gene interaction) and with environmental factors (gene-environment interaction) has a crucial role in the development of the pathology. Moreover, the diversity of ethnic background may be a possible bias in such research. In the light of these considerations we selected Caucasian, Italian subjects only, and we constructed a literature based genetic risk score for skin aging with the aim to evaluate the contribution of individual genetic variability to skin aging. Prior skin aging studies have analyzed intrinsic and extrinsic skin aging parameters, believed to reflect genetic and environmental factors contributing to skin aging feature. Heritability analyses in twins have shown that genetic component of skin deterioration process accounts for about 60% [3]. In recent years, research on genetic polymorphisms indicate that Genetic Risk Scores (GRSs) allow the composite assessment of genetic risk in complex traits. Although some authors have expressed doubts as to whether a candidate gene approach can ever add significantly to risk prediction, because of the modest impact on risk, and the apparent inconsistency of effect, other authors demonstrate that, depending on the prevalence and heritability of the disease, few genetic variants may have a strong predictive power. Our results indicate that the use of the genetic risk score including 8single nucleotide polymorphisms This work is partly presented at International Conference on Aesthetic Medicine and Cosmetology, May 21-22 2018A¢Â”‚Singapore Vol.4 No.2 Extended Abstract Skin Diseases & Skin Care 2019 involved in aging process aspreviously described in literature, could be promising to predict skinproperties evolution and address antiA¢Â€Âaging and skin treatment againstspecific metabolic target. Keywords

(1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

Melanoma is a severe form of cancer, resistant to conventional therapies. According to in vitro studies, sulforaphane, a dietary component, has been considered a promising antineoplastic candidate. The present study analyzes the in vitro biological effects of sulforaphane in A375 melanoma cell line with or without the addition of Nerve Growth Factor. For the first time, our results show that a supplementation of Nerve Growth Factor partially reverses the sulforaphane-induced: i) inhibition of cell migration, ii) pro apoptotic changes in cell cycle and iii) modulation of active caspase-3. Furthermore, we report the sulforaphane-induced modulation in the expression of Nerve Growth Factor receptors TrKA and p75NTR, shifting their ratio from pro survival to pro apoptotic. In conclusion, the present study evidences that in vivo the antineoplastic effects of sulforaphane may be reduced by the contemporaneous presence of other biological elements such as Nerve Growth Factor and it contributes to a better definition of the real in vivo potentiality of sulforaphane as antineoplastic candidate.

Photoageing represents the addition of extrinsic chronic ultraviolet radiation induced damage on intrinsic aging and accounts for most age-associated changes in skin appearance. The skin contains numerous endogenous antioxidants to help provide protection from reactive oxidative species generated during normal cellular metabolism. However, overexposure to UV radiation can lead to a significant reduction in the antioxidant supply accompanied by an increase of proinflammatory cytokines leading to accelerated oxidative damage. Photochemoprevention with botanical antioxidants is a strategy shown to be capable of blunting the damaging effects of ultraviolet radiation. Together with antioxidant properties, dietary flavonoids and their metabolites may modulate basic cellular signal transduction pathways leading to anti-proliferative, anti-aging and immune modulating responses. Here, we describe the effects of bergamot polyphenolic fraction (38% BPF), a highly concentrated extract of flavonoids derived from the citrus bergamot fruit, able to inhibit UVB mediated decrease in cell viability, overexpression of inflammatory cytokine biomarker interleukin-1beta (IL-1β), telomere shortening and decreases in telomerase activity.

Purpose Human melanoma is a highly aggressive incurable cancer due to intrinsic cellular resistance to apoptosis, reprogramming, proliferation and survival during tumour progression. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, plays a role in carcinogenesis in many cancer types. However, the cytotoxic molecular mechanisms and gene expression profiles promoted by SFN in human melanoma remain unknown. Methods Three different cell lines were used: two human melanoma A375 and 501MEL and human epidermal melanocytes (HEMa). Cell viability and proliferation, cell cycle analysis, cell migration and invasion and protein expression and phosphorylation status of Akt and p53 upon SFN treatment were determined. RNA-seq of A375 was performed at different time points after SFN treatment. Results We demonstrated that SFN strongly decreased cell viability and proliferation, induced G2/M cell cycle arrest, promoted apoptosis through the activation of caspases 3, 8, 9 and hampered migration and invasion abilities in the melanoma cell lines. Remarkably, HEMa cells were not affected by SFN treatment. Transcriptomic analysis revealed regulation of genes involved in response to stress, apoptosis/cell death and metabolic processes. SFN upregulated the expression of pro-apoptotic genes, such as p53, BAX, PUMA, FAS and MDM2; promoted cell cycle inhibition and growth arrest by upregulating EGR1, GADD45B, ATF3 and CDKN1A; and simultaneously acted as a potent inhibitor of genotoxicity by launching the stress-inducible protein network (HMOX1, HSPA1A, HSPA6, SOD1). Conclusion Overall, the data show that SFN cytotoxicity in melanoma derives from complex and concurrent mechanisms during carcinogenesis, which makes it a promising cancer prevention agent. Electronic supplementary material The online version of this article (doi:10.1007/s00394-017-1527-7) contains supplementary material, which is available to authorized users.

Background Head and neck melanoma is a clinical challenge. Indeed, cutaneous head and neck melanoma shows a worse prognosis in comparison to melanomas of other body sites. Although the emphasis on facial cosmetic preservation plays a pivotal role in comparison to other body areas, specific Facial Aesthetic Units (FAU) could also play a key role in the prognostic evaluation of the malignancy. Methods The aim of the current study was to evaluate the general outcome and clinicopathological features of head and neck melanoma and to detect prognostic differences according to each FAU. The Kaplan-Meier product was used to calculate survival curves, while Cox proportional-hazard regression was performed to evaluate the predictive value of each FAU. Results A total of 221 head and neck melanoma patients was included in our analysis. In the nasal FAU, we found a high rate of local recurrence, which affected significantly disease-free survival. The worse prognosis was observed in melanoma of the scalp, which showed a greater tendency to skip metastases in internal organs. Moreover, we found that scalp showed a low incidence of non-melanoma skin cancers, if compared to other FAU, highlighting that the scalp local milieu might play a more prominent role in melanoma biology than chronic UV exposition. Conclusions Although FAUs have an aesthetic function, they could also play a role in the evaluation and follow-up of melanoma.

No abstract available

Ultraviolet rays are one of the leading factors in the development of melanoma (MM); however, ultraviolet rays seem not to play a role in non-sun-exposed MM, where systemic immunosuppression, anatomical, and physiological features may contribute toward the development of the malignancy. Our aim was to evaluate vitamin D receptor (VDR) expression in shield-site melanoma (ST-MM) and non-shield-site melanoma (NST-MM) to find features that could explain the different biological behavior of MM according to the area of onset. We reviewed 118 specimens of MM. VDR expression was assayed using immunohistochemistry by dividing the specimens according to the anatomical area. We included MM of the soles, feet, hands, gluteus, scrotum, skin of the penile shaft, and large vaginal labia in the ST-MM group. The NST-MM group was divided into two main categories: NST-MM of chronic sun-exposed areas, including MM of the face, scalp, neck, back of the hands, and NST-MM of intermittent sun-exposed areas, including MM of the trunk, lower, and upper limbs. In shield sites, 66.67% of MMs showed VDR expression; in intermittent sun-exposed areas, 33.3% showed VDR expression; and in chronic sun-exposed areas, only 4.66% showed VDR expression. A similar behavior was observed for Breslow's thickness, where VDR staining intensity was higher in thicker lesions, ranging between 60 and 100%. We found that VDR expression decreased from ST-MM to NST-MM. These findings confirm the hypothesis that different pathways are involved in ST-MM and NST-MM.

Psoriasis is a chronic inflammatory skin disease affecting 2%–3% of the population. The wide range of drugs currently available for its treatment could be associated, in the long term, with organ toxicity and adverse events, thus, clinical monitoring throughout treatment is required. This investigator-initiated trial (IIT) evaluated the efficacy and the safety of a vitamin B12-containing ointment in comparison with glycerol-petrolatum-based emollient cream used twice a day to treat mild-to-moderate plaque psoriasis for a period over 12 weeks followed by a wash-out observation period of 4 weeks. This study was conducted as a randomized, controlled, single-blind, intra-patient left- to right-side trial comparing the efficacy and safety of vitamin B12-containing ointment (M-treatment) with a glycerol-petrolatum-based emollient cream (C-treatment). The Psoriasis Area Severity Index (PASI) was determined at baseline (T0), at time points T2 (14 days), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks) and 4 weeks after the end of the wash-out period (F1). In total, 24 patients with plaque psoriasis were randomized to receive left- or right-side treatment with B12ointment. From time point T2 to time point F1, there was a statistically significant difference in PASI reduction between M-treatment side and C-treatment side. At time point T 12, the difference between the mean reductions from baseline PASI scores by 5.92 ± 2.49 (87, 6%) in the M-treatment side versus 1.08 ± 1.02 (23, 1%) C-treatment side was statistically highly significant ( PWex 12ointment will represent a new concrete therapy option and should be considered in the update of therapeutic algorithm for the treatment of psoriasis

Introduction: The epidermal growth factor receptor inhibitors (EGFRIs), cetuximab and panitumumab, represent an effective treatment option for patients affected by metastatic colorectal cancer (mCRC); furthermore, they are relatively devoid of systemic toxicities, which are commonly observed with standard cytotoxic chemotherapy. However, the majority of patients treated with these monoclonal antibodies (mAbs), will experience dermatologic toxicities, most notably the papulopustular skin rash, which can impact quality-of-life and affect adherence to therapy. This paper reviews the most recent practices in the management of skin rash related to anti-epidermal growth factor receptor (EGFR) mAbs, cetuximab and panitumumab, in the treatment of mCRC. Materials and Methods: We reviewed relevant literature regarding dermatologic toxicities associated with anti-EGFR mAbs in order to give important indications about prevention and reactive treatment of skin rash. Results: Two case reports were presented to show how skin rash could hamper mAb EGFRIs use in clinical practice, underscoring the need of implementing a comprehensive management strategy of skin toxicity in order to promote patients' compliance with anti-EGFR therapy and maintain quality-of-life. Based on randomized data, recent guidelines established by the Multinational Association for Supportive Care in Cancer Skin Toxicity Study Group suggest that prophylactic use of oral doxycycline or minocycline reduces the risk and severity of skin rash, improving clinical outcomes. Conclusions: At the start of treatment with cetuximab and panitumumab, the proper patient education about the skin rash associated with these mAbs and the implementation of a pre-emptive, comprehensive skin toxicity program significantly contribute to improve adherence to therapy, optimize anti-EGFR therapy and maintain quality-of-life.

Pitted keratolysis (PK) is a plantar skin disorder mainly caused by coryneform bacteria. A common treatment consists of the topical use of erythromycin. Hyperhidrosis is considered a predisposing factor for bacterial proliferation and, consequently, for the onset of PK. The aim of this study was to evaluate the relationship between PK erythromycin and hyperhidrosis. All patients with PK seen in Sant'Andrea Hospital, between January 2009 and December 2011, were collected. PK was clinically and microscopically diagnosed. All patients underwent only topical treatment with erythromycin 3% gel twice daily. At the beginning of the study and after 5 and 10 days of treatment, a clinical evaluation and a gravimetric measurement of plantar sweating were assessed. A total of 97 patients were diagnosed as PK and were included in the study. Gravimetric measurements showed that in 94 of 97 examined patients (96.90%) at the time of the diagnosis, there was a bilateral excessive sweating occurring specifically in the areas affected by PK. After 10 days of antibiotic therapy, hyperhidrosis regressed together with the clinical manifestations. According to these data, we hypothesize that hyperhidrosis is due to an eccrine sweat gland hyperfunction, probably secondary to bacterial infection.

Imatinib mesylate (IM) represents the first-line treatment of patients with chronic myeloid leukemia (CLM) or gastrointestinal stromal tumor (GIST). It presents several side effects. However, less than 10% are nonhematologic including nausea, vomiting, diarrhea, muscle cramps, and cutaneous reactions. The aim of our study was to identify data regarding IM cutaneous adverse effects (AEs) to improve the clinical diagnosis and management of the more frequent side effects. Skin examination should be done before and during IM treatment so that AEs can be diagnosed and treated early with less impact on chemotherapy treatments and on the quality of life of the patient.

Extracutaneous melanoma (ECM) is a very rare malignancy and its biology differs from that of cutaneous melanoma. Residential studies can offer an important contribution to the study of this disease.We characterized the distribution of ECM according to residential and demographic baseline characteristics. We computer-searched patients that removed an ECM, and we analyzed all demographic and residential parameters. Disease free survival (DFS), date of death or last follow-ups were evaluated. The same parameters were analyzed using hazards-regression. Finally, we used the multiple regressions between DFS and the predictors.A total of 44 ECM patients were included in our analysis. Median DFS was of 10 months; at Log-Rank Test and Cox-hazard regression, the variable age (P0.01; P0.004) and latitude (P0.02; P0.006) reached a statistical significance; at multiple logistic regression, the significance was instead maintained only for the variable age. General OS was of 42 months at Log-Rank Test age (P0.001), as well as latitude (P0.006) maintained its significance at hazard-regression.Demographic and residential aspects can play an important role in the study of this rare disease, supporting the assumption that ECM are generated by processes actually unknown, as demonstrated in our results compared with those of the literature.

BACKGROUND: Mycosis fungoides (MF) is an indolent primary cutaneous T-cell lymphoma. To the authors' knowledge, no data currently are available regarding the evolution over time of the risk of developing specific pathways of disease progression. METHODS: This retrospective study analyzed 1422 patients with MF who were diagnosed and followed from 1975 through 2010 in 27 Italian Study Group for Cutaneous Lymphoma centers. The primary objectives were to ascertain the time course, pathways, and hazards risk trends of cutaneous/extracutaneous disease progression; to evaluate whether different tumor-lymph node-metastasis-blood (TNMB) stages have different pathways of disease progression; and to analyze differences between tumor-stage and erythrodermic MF with regard to clinical onset, disease evolution, and prognosis. The secondary objective was to provide a further validation for the revised International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. RESULTS: The median follow-up was 14.5 years; stage progression occurred in 29.7% of patients and blood involvement was the most frequent extracutaneous site of disease progression. Patients with stage IA to stage IB disease demonstrated a steady low annual incidence of disease progression to tumor-stage (1%-2%); patients with stage IIA disease had a higher risk within the first years (up to 9.4%). Erythroderma evolved with a significantly higher frequency from patches/plaques (13.9%/28.2%) than tumors (P = .028 and P = .013, respectively). Hazards rates of extracutaneous involvement were low (< 1%). The T-score was found to be associated with extracutaneous involvement site, tumor-stage disease with lymph node/visceral lesions, and erythroderma with blood involvement. TNMB classification and stage progression resulted as independent prognostic variables being detected on multivariate analysis; the type of extracutaneous involvement was found to affect survival . CONCLUSIONS: The data from the current study support the need for a stage-tailored follow-up, suggest that the classification of tumor-stage disease at a stage below erythroderma could be modified, and offer a further validation for the revised TNMB classification. Cancer 2012. © 2012 American Cancer Society.

In the literature, there are some papers report- ing on patients with metastatic melanoma from an unknown primary lesion (MUP). The pathogenesis of this phenomenon and the prognosis of these patients are still debatable. Therefore, we reviewed our casistics on MUP patients. We identified 24 MUP patients out of all patients registered into a melanoma database from June 1996 to June 2011. The incidence was 1.4 %. We compared the survival rate of all patients with MUP stage III-IV with all patients with metastatic melanoma known primary (MMKP) stage III-IV observing a clear survival improvement for MUP patients in front of MMKP patients (p \ 0.01). In a second instance, we compared stage III MUP patients with only lymph nodal involvement with stage III MMKP patients with only lymph nodal involve- ment, and again we found statistically significant better survival for MUP patients (p \ 0.05). In this retrospective study, the number of lymph nodes involved (p = 0.8), the sex (p = 0.9), and S100 value (p = 0.2) were not statisti- cally relevant for prognosis. The better prognosis for these patients is very similar to better survival rate for metastatic melanoma patients and vitiligo. This correlation may be in accord with the hypothesis of a regression of primary lesion by immunological system of the host and also the median age of patients at the time of diagnosis, commonly older than melanoma patients, may correspond to a long period of immunological interferences between the host and the melanoma disease.

In the last years the nature of initiating melanoma cells has been discussed and the melanoma stem cell theory has been proposed as and alternative and/or supplemental view of newborning melanoma cells. It has been described that melanoma cells derived from metastatic melanoma specimens as well as melanoma cell lines are able to grow in an embryonic stem cell-based media and these melanoma stem-like cells possess capacity of self-renewal and high tumorigenicity. In 2005 the first evidence of a stem-cell like population existence in human melanoma has been provided. CD133 or prominin-1 is one of most studied marker of staminality expressed by melanoma cells; specifically, the down regulation of CD133 leads to a reduced cell capacity to metastatize. Nevertheless, there is disagreement concerning the constant presence of CD133þ cells in primary and metastatic melanomas. ABCB5, the third member of the human P-gp family, is a rhodamine and doxorubicin efflux transporter, identified as a novel drug transporter involved in drugresistance in human malignant melanoma. ABCB5 was found to be specifically expressed on CD133þ tumor

Goal: Psoriasis is a chronic skin disease which is very common in the population and requires frequent clinical and pharmacological treatment. In the following, a study based on Fourier transform infrared spectroscopy analyzing saliva proteomic components in psoriatic patients against diabetic patients and a control group is presented. Clinical analysis showed a prominent amide II band, at around 1545 cm−1, and the composition of the amide I band, at around 1647 cm−1, allowing us to distinguish the infrared salivary signature of psoriatic and diabetic patients from the control group and even from patients with different kinds of psoriasis. Moreover, results highlighted existing differences in the secondary structure composition of proteins between psoriatic and diabetic patients as compared to the control group. In fact, the saliva spectra of the control group and that of the palmoplantar psoriatic patients differ from plaque psoriasis and diabetic patient spectra because of the absence of the amide II band and the presence of different secondary protein-structure conformations.

Pseudoporphyria refers to a rare bullous dermatosis characterized by the clinical and histological features of porfiria cutanea tarda without abnormalities in porphyrin metabolism. The pathogenesis is heterogeneous and several exogenous factors may promote the bullous lesion formation, including medications, end stage renal disease, dialysis and tanning beds. Regarding treatment of this condition, in literature different therapy have been reported, such as glutathione and his precursor N-acetylcysteine, which presents anti-oxidant properties; however even more toxic drugs, such as chloroquine, are used. Moreover, in patients with drug-induced PP discontinuation of the offending agent, if possible, is a crucial aspect of the clinical management. We report two cases of dialysis patients presenting blisters on extremities, which healed with the avoidance of UV exposure and oral Vitamin D supplementation. Interestingly Vitamin D despite the lack of antioxidant properties led to a completely resolution of PP in both our patients within 30 days. A possible explanation of this finding is that Vitamin D, playing a key role in the regulation of serum Ca2+, can modulated cadherin-cadherin interactions and led to healing of pseudoporphyria bullous lesions. Finally we highlight the prominent role of UV-exposure in PP elicitation thus a good photoprotection is essential for all patients with pseudoporphyria.

Background: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. Objective: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. Methods: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. Results: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. Conclusions: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

We described the case of 45 years-old woman affected by a flagellate dermatitis arisen immediately after having a bath in sulfurous thermal water. Such dermopathy resolved after a common scratching of the lesions by the patient, so that the possible pathogenetic mechanism to explain the resolution of the lesions is the mechanical removal of cornified cell layer. After six months follow-up, the patient is in good conditions, without relapses of the flagellate dermatitis.

Summary Background An association between autoimmune disease and malignant melanoma (MM) has often been reported in the literature as a positive prognostic factor for MM. Consequently, we evaluated the influence of different autoimmune diseases on the prognosis of MM. Aim To evaluate the prognosis of patients with MM who also had an autoimmune disorder, whether tumour-associated, paraneoplastic or drug-induced. Methods Autoimmune diseases were classified and analysed as tumour-associated, paraneoplastic or drug-induced. Patients were enrolled according to their clinicopathological features and matched with control groups. Kaplan–Meier analysis was used to estimate disease-free survival (DFS) and overall survival (OS), and log-rank test was used to evaluate differences between the survival curves. Results In total, 49 patients with MM and tumour-associated autoimmune disease were included in our analysis. No case of paraneoplastic autoimmune disease was detected. The survival analyses showed a range of results, from a worsening of DFS and OS to a lack of any difference. In a second analysis, we separately analysed patients who developed autoimmune disorders after starting adjuvant therapy with interferon-α; we did not find significant differences between these patients and the untreated patients. Conclusions Autoimmune disease, whether tumour-associated or drug-induced, was not associated with better prognosis in patients with MM. The results suggest that the reported relationship between autoimmunity and MM may be a result of individual variation in sensitivity to the autoimmune disease, the tumour or the treatments.

Intermittent sun exposure and sunburns are strongly related to the development of melanoma (MM); however, MM can also arise in non-sun exposed areas, where other biological pathways may cause the disease, with different outcomes. At the same time, evidences of serum levels of vitamin D in melanoma patients according to sun-exposed or not-sun-exposed areas are still lacking, especially if compared with the percentage of BRAF mutation. We performed a retrospective analysis with patients registered in our electronic database and an observational study in patients with a recent diagnosis of MM. Performing Kaplan–Meier product and log-rank test, median disease-free survival was 78 months in non-shield-sites (NST-MM) patients and 20.5 months in shield-sites (ST-MM) patients (p

Nodular histotype represents the condition that is mostly associated with diagnosis of thick melanoma.The objectives were to evaluate variables associated with and pattern of detection of nodular melanomas and to investigate variables associated with early diagnosis in accordance with histotype (nodular vs. superficial spreading melanomas).From the original data set of 816 melanomas, all the invasive lesions classified as superficial spreading (n=500) and nodular (n=93) melanomas were considered for the study. A multivariate logistic analysis was performed. Results. Nodular melanomas did not significantly differ from superficial spreading melanomas regarding sex, anatomic site, number of whole-body nevi, and the presence of atypical nevi. As expected, nodular melanomas were represented by a higher percentage of thick (2 mm) lesions compared to superficial spreading melanomas (64.5% vs. 9.6%, p0.001). The pattern of detection significantly differed between nodular and superficial spreading melanomas, the former being more frequently self-detected (44.1% vs. 38.0%) or detected by the family doctor (34.4% vs. 11.4%). Female sex, high level of education, and detection made by a dermatologist had an independent, protective effect against late (1 mm in thickness) diagnosis in superficial spreading melanomas. No protective variable associated with nodular melanomas was found.Patterns of detection for nodular melanomas significantly differ from those for superficial spreading melanomas. For superficial spreading, but not for nodular, melanomas, variables associated with protective effect against late diagnosis can be identified.

Purpose: The expression of apoptosis-related genes, such as survivin, bcl-2, bcl-X, and bax, has been evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry in sentinel lymph nodes (SLNs) from melanoma patients and then correlated to the outcome of patients. Patients and Methods: Thirty-six SLNs were examined. After RNA extraction, an RT-PCR followed by Southern blot hybridization was performed to detect survivin, bcl-2, bcl-X, and bax mRNA. bcl-2, survivin, and bax gene expression was evaluated, whenever possible, also by immunohistochemistry at the protein level. Results: We found a significant correlation (P < .005) between survivin expression and outcome of patients; in fact, 61.5% of patients expressing survivin gene progressed or died because of the disease, whereas 38.5% are currently disease-free. Among patients negative for survivin expression, 100% are disease-free after a median follow-up time of 52.9 months. We did not find a significant correlation between bcl-2, bax, and bcl-X gene expression and outcome of patients. In fact, these genes were found equally expressed in patients with disease progression and in disease-free patients. Conclusion: Our findings show a variable expression of apoptosis-related genes in SLNs of melanoma patients; more interestingly, we found that survivin expression correlates to outcome of patients in a statistically significant way, whereas the expression of other genes, such as bcl-2, bax, and bcl-X, did not seem to correlate to progression of disease. We suggest that the detection of survivin gene expression by RT-PCR in SLNs may be a useful prognostic indicator.

Interferon alpha (IFNalpha) is the most used adjuvant treatment in clinical practice for melanoma (MEL) high-medium risk patients; however, the use of IFNalpha has yielded conflicting data on Overall Survival (OS) and disease free survival (DFS) rates. Starting from these considerations, we carried out an analysis on our MEL patients who received adjuvant IFNalpha therapy, in order to identify possible predictors for their outcome. A total of 140 patients were included in our analysis. Patients with Breslow thickness#8804;2.00 mm presented a significantly longer mean DFS than patients with Breslow#8805;2.01 mm (p = 0.01). Using non- parametric Spearman’s Coefficient test we found association between DFS and Breslow thickness (p0.001) and between DFS and ulceration (p = 0.03). Performing Multiple Regression test, Breslow thickness (p0.001) remained the only statistically significant predictor. From the OS analysis we found that patients with lower Breslow values#8804; 2.00 mm (p0.0001), and absence of ulceration (p0.004) showed a significantly better long-term survival. From the current analysis we found that the use of low dose IFNalpha is justified only for cutaneous melanoma#8804; 4.01 mm that was not ulcerated; patients with Breslow#8805; 4.01 mm, in our opinion, should not carry out adjuvant treatment with low dose IFNalpha, because its side effects could be higher than the its benefits.

Skin manifestations are often associated with systemic autoimmune diseases (SAD). Some SAD, such as systemic lupus erythematosus, psoriatic arthritis and scleroderma display pathognomonic dermatological features, whereas other systemic diseases such as sarcoidosis, vasculitis and rheumatoid arthritis can present with non-specific skin manifestations that range from erythema nodosum to necrotic lesions. Here we report the case of a 25-year-old man with uveitis, polyarthrirtis, pulmonary involvement, nephrotic syndrome, cutaneous granuloma and pneumonia by E. coli.

Background: The lung is the second most common site for metastatic malignant melanoma, with a poor prognosis. In this regard, identify clinicopathological predictors for Melanoma Lung Metastases (MLM) plays a pivotal role in clinical practice. Methods: We computer-searched the clinical records of all our patients registered in our melanoma database to identify patients that presented MLM. Kaplan-Meier product was used to estimate time to MELANOMA LUNG METASTASES (TMLM) and Overall Survival (OS); while the log-rank test was used to evaluate differences between the survival curves. Cox proportional hazards regression was performed in the analysis between clinicopathological features of the primary tumor and MLM. Results: A total of 63 patients with MLM were included in our analysis. Median TMLM was 27.4 months, while median OS was 55.5 months, with a Median Lung Metastases Survival (MLMS) of 10 months. Melanoma patients with a primary axial tumor (p

Basal cell carcinoma (BCC) is the most common skin malignant neoplasm in humans. Its localization and its clinical-pathological aspects are fundamental for the treatment and the outcome of these tumors. We wanted to verify if different clinical-pathological subtypes of BCC may be present with different frequencies on single skin areas.Three hundred six patients affected by BCC seen in Sant'Andrea Hospital, U.O.C. Dermatology, NESMOS Department, Faculty of Medicine, University of Rome "Sapienza", from January 2008 to December 2010, were retrospectively included in this study. Findings from all patients were tabulated and analyzed to characterize the clinical-pathological aspects of BCC according to their anatomic localization. We considered the following clinical subtypes of BCC, nodular, superficial, sclerodermiform, pearly and ulcerative.One hundred ninety-seven out of 306 patients (64.4%) were localized on the head, 6 (1.9%) on the neck, 73 patients (23.9%) on the trunk, 2 (0.6%) on the perineum, 4 (1.3%) on upper limbs and 24 (7.9%) on legs. On the head BCC were mostly nodular (44.7%). On the trunk they were mostly superficial (34.3%). BCC on legs were ulcerative in all the 24 patients.Our data confirm that BCC may have different clinical-pathological aspects on single skin areas. Interestingly in our casistic BCC on the legs were present in an uncommon high percentage. They presented as ulcerative lesions and this fact leads to conclude that in every patient presenting a chronic ulcer on the leg with difficulty to be cured a biopsy is mandatory to put in evidence the possible presence of BCC and consequently to perform the correct surgical treatment to obtain a complete response for the patient.